The Center for Environmental Health at Jackson State University (JSU) has recently been funded for a second 5-year cycle starting July 01, 2003. The Center has been structured to develop and sustain an adequate biomedical research infrastructure, and to serve as a platform to nurture and emphasize interdisciplinary research programs in the area of environmental health. So far, the RCMI support has made a tremendous impact on the development of biomedical research, and has significantly contributed to the recent ranking of JSU as a comprehensive, research-intensive institution according to the Carnegie classification. Through the RCMI support, six multi-user core research facilities have been established, three new biomedical research faculty have been hired. The specific aims of Center are: 1) to provide the research infrastructure and support needed to facilitate the research of the Center's investigators, through enhancement of existing multi-user core facilities; 2) to strengthen and enhance opportunities for faculty development, facility access, major equipment needs, and technology transfer; 3) to continue to foster and enhance collaborative research efforts among faculty and scientists from JSU, other institutions of higher Learning, and national laboratories; 4) to increase the pool of highly trained minority professionals in environmental health; 5) to promote, coordinate and enhance broad-based competitive research capabilities and resources at JSU, thereby increasing the quality of biomedical research programs; and 6) to serve as a resource center for the environmental health community and other HBCUs in Mississippi. Addressing the Center's needs in terms of infrastructure enhancement, and faculty development, will provide the opportunity for the institution to become more competitive nationally within the mainstream of research and development. The main focus of this proposal is to provide faculty development (FD) opportunities to two promising junior faculty who have demonstrated a great potential for biomedical research. A comprehensive plan has been developed to maximize productivity of these two individuals in all important areas of biomedical research training and academic excellence. Each of these two FD candidates has developed and submitted an independent research proposal with its own merit. Each has been paired with senior faculty members/established scientists who serve as [mentors and provide them with guidance and advice needed for professional growth. Coupled with the development land implementation of specific biomedical research projects, these activities will certainly provide excellent opportunities to the FD candidates to enhance their scientific skills in all aspects of biomedical research, as well as their competitiveness in grantsmanship. Achieving independence from the RCMI program by writing successful RO-1 grants is therefore the ultimate goal for this FD initiative. [unreadable] [unreadable] ACTIVITY 1: SPIROISOXAZOLINES, BREAST CANCER, AND ESTROGEN [unreadable] RECEPTORS [unreadable] [unreadable] DESCRIPTION (provided by applicant): The Research Center in Minority Institutions (RCMI) at Jackson State University (JSU) focuses on developing and sustaining biomedical research projects through continuous improvement of research infrastructure, research faculty, and support personnel. In this project, the FD Candidate will be mentored by senior level faculty and seasoned scientists who will provide him the needed guidance and assistance in all important areas of biomedical research and academic excellence. The FD candidate will be taking short courses in microbiology and computational chemistry. The FD candidate plans to take the microbiology short course at a research conference, and the computational chemistry short course will be taken at JSU. Both courses will increase the FD candidate's understanding of estrogen receptors and the utilization of computational ligand binding studies of breast tissue estrogen receptors with potential competitive antagonists. The proposed research focuses on breast cancer, its relationship to the natural product, 11- deoxyfistularin-3, and estrogen receptors. Recently, the natural product 11-deoxyfistularin-3 was found to be cytotoxic towards estrogen dependant MCF-7 breast cancer cells (LD50 = 17 mg/L). One of the overall goals of the research project is to use 11-deoxyfistularin-3 as a scaffold for the design of alternative compounds that are potentially cytotoxic towards breast cancer tissue through a combination of synthetic organic chemistry and computational ligand binding studies. The other goal is also to determine if 11- deoxyfistularin-3 is cytotoxic against breast cancer resistant (MDA-MB-231) breast cancer cell lines, and if 11-deoxyfistularin-3 is not cytotoxic against these cells, is the activity the natural product in MCF-7 cells related to its binding to estrogen receptors. Spiroisoxazolines are present in 11-deoxyfistularin-3, and a facile synthetic method of these ring systems along with estrogen receptor ligand binding studies and in vitro assays of these synthesized spiroisoxazolines against both types of breast cancer cells will be explored. The proposed didactic and research activities will achieve the RCMI and FD program goals through enhancing the skills of the FD candidate which will allow the FD candidate to become an independent biomedical researcher. [unreadable] [unreadable]